The proposed study is concerned with an evaluation of the antiarrhythmic activity of a series of compounds synthesized in our Medicinal Chemistry Laboratories. The drugs in question are characterized by being quaternary ammonium compounds. Each of the agents will be assessed for its actions against digitalis-induced arrhythmias as well as rhythm disorders associated with experimentally-induced myocardial ischemia and/or infarction. All agents will be examined for their ability to protect the heart against the development of ventricular fibrillation by studying the drugs in animals subjected to periods of myocardial ischemia followed by abrupt reperfusion and by studying the influence of the drugs upon the electrical ventricular fibrillation threshold. The detailed cardiovascular pharmacology of these agents will be explored. Studies will be carried out on the electrophysiologic effects of the quarternary-ammonium drugs in the ischemic and normal canine myocardium in an effort to determine their possible mechanism of action and to compare their actions to the more commonly employed antiarrhythmic drugs. An attempt will be made to better understand the relationships between chemical structure and antiarrhythmic and/or antifibrillatory activity. BIBLIOGRAPHIC REFERENCES: Lucchesi, B.R. and Lomas, T.E.: The cardiac effects of the oral hypoglycemic agent glyburide. In Micronase (Glyburide) Pharmacological and Clinical Evaluation. Ed. by Harold Rifkin. Excerpta Medica, 1975. Princeton, N.J., pp. 91-104. Lucchesi, B.R., Burmeister, W.E., Lomas, T.E. and Abrams, G.D.: Ischemic changes in the canine heart as affected by the dimethyl quaternary analog of propranolol, UM-272 (SC-27761). J. Pharmacol. Exp. Ther. (in press, 1976).